Rex A. Hess
Professor, Veterinary Biosciences
Professor, Veterinary Program in Agriculture
Professional Interests: My laboratory conducts research in the areas of male reproductive and stem cell biology, endocrinology, and toxicology, with the following specific interests: spermatogenesis, testicular growth and development, the role of estrogens in male reproduction and regulation of spermatogonial stem cells.
Estrogen in the male. A major discovery was published in Nature (1997) 390, 509-512, showing for the first time an important function for estrogen in the male reproductive tract. Estrogen is considered the "female" hormone, whereas testosterone is considered the "male" hormone. However, both hormones are present in both sexes. Thus, sexual distinctions are not qualitative differences, but rather due to quantitative divergence in hormone concentrations and differential expressions of steroid hormone receptors. In males, estrogen is present in low concentrations in blood, but can be extraordinarily high in semen and as high as 250 pg/ml in rete testis fluids, which is higher than serum estradiol in the female. It is well known that male reproductive tissues express estrogen receptors (J of Andrology). We have now determined that estrogen regulates expression of the Na + /H + exchanger-3 (NHE3) and the rate of (22)Na + transport, sensitive to a NHE3 inhibitor. This was the first demonstration of a physiological function for oestrogen in male reproductive organs. Disruption of this essential function causes sperm to enter the epididymis diluted, rather than concentrated, resulting in infertility. References
Spermatogonial stem cells. A major discovery was published in Nature (2005) 436:1030, showing that ERM, an Ets Related Molecule and Pea3 subfamily, that is expressed in Sertoli cells of the testis, is essential for the regulation of spermatogonial stem cell self-renewal. ERM-/- males undergo the first wave of spermatogenesis, which appears to be normal, but subsequent waves are lost through maturation depletion of germ cells, resulting in sterility. Testes from ERM-/- mice aged 3 months or older exhibit complete seminiferous tubular atrophy, characterized by depletion of all germ cells, but retention of Sertoli cells. This defect is independent of GDNF, a Sertoli cell derived growth factor that is also required for spermatogonial stem cell self-renewal. Thus, Sertoli cell derived factor(s) under the regulation of ERM control the continuation of spermatogenesis through the self-renewal of spermatogonial stem cells.
Toxicant effects of benomyl on male reproduction. . Testicular
and efferent ductule effects of carbendazim (methyl 2-benzimidazole carbamate),
a metabolite of the fungicide benomyl, were determined in the adult rat after a single exposure. Effects were first seen beginning at 8 h post-exposure as an increase in testis weight; then decreases in testicular spermatid numbers, epididymal sperm reserves, and in the percentage of morphologically normal cauda sperm. A dose-dependent increase in testicular weight at 2 days post-treatment was accompanied by increases in seminiferous tubular diameter, and excessive loss of immature germ cells in a stage-dependent manner and eventual atrophy. There was also a dose dependent increased incidence of occlusions in the efferent ductules. ?Thus, the long-term effects of benomyl on the testis are due to back-pressure of fluid that leads to seminiferous tubular atrophy.
Selected Publications:
Ruz R, Gregory M, Smith CE, Cyr DG, Lubahn DB, Hess RA and Hermo L. (2006) Expression of aquaporins in the efferent ductules, sperm counts, and sperm motility in estrogen receptor-alpha deficient mice fed lab chow versus casein. Mol Reprod Dev. 73:226-237.
Holsberger DR, Buchold GM, Leal MC, Kiesewetter SE, O'Brien DA, Hess RA, Franca LR, Kiyokawa H and Cooke PS. (2005) Cell-cycle inhibitors p27Kip1 and p21Cip1 regulate murine Sertoli cell proliferation. Biol Reprod. 72:1429-36.
Chen C, Ouyang W, Grigura V, Zhou Q, Carnes K, Lim H, Zhao G-Q, Arber S, Kurpios N, Murphy TL, Cheng AM, Hassell JA, Chandrashekar V, Hofmann M-C, Hess RA and Murphy KM. (2005) ERM is required for transcriptional control of the spermatogonial stem cell niche. Nature. 436:1030-1034.
Oliveira CA, Carnes K, França LR, Hermo L, Hess RA. (2005) Aquaporin-1 and -9 are differentially regulated by estrogen in the efferent ductule epithelium and initial segment of the epididymis. Biology of the Cell. 97:385-895. ( This is a special edition dedicated to Peter Agre, who received the 2003 Nobel Prize in Chemistry for his discovery of water channels in membranes. All manuscript were submitted after special invitation by the editor.)
Oliveira CA, Mahecha GA , Carnes K, Prins GS, Saunders PT, Franca LR and Hess RA. (2004) Differential hormonal regulation of estrogen receptors ERalpha and ERbeta and androgen receptor expression in rat efferent ductules. Reproduction 128:73-86.
Oliveira C, Nie R, Carnes K, Franca LR, Prins GS, Saunders PTK and Hess RA. (2003) The antiestrogen ICI 182,780 decreases the expression of estrogen receptor-alpha but has no effect on estrogen receptor-beta and androgen receptor in rat efferent ductules. Reprod Biol Endocrinol. 1, 75.
Zhou Q, Clarke L, Nie R, Carnes K, Lai LW, Lien YH, Verkman A, Lubahn D, Fisher JS, Katzenellenbogen BS and Hess RA. (2001) From the Cover: Estrogen action and male fertility: Roles of the sodium/hydrogen exchanger-3 and fluid reabsorption in reproductive tract function. Proc Natl Acad Sci U S A. 98, 14132-14137.
Hess RA and Nakai M. (2000) Histopathology of the male reproductive system induced by the fungicide benomyl. Histol. Histopathol. 15:207-224.
Hess RA. (2000) Oestrogen in fluid transport and reabsorption in efferent ducts of the male reproductive tract. Reviews of Reproduction. 5:84-92.
